NAD+ enhancer ameliorates DSS-induced colitis
in mice
To investigate the anti-inflammatory effect of LMT503 on IBD in
vivo , mouse DSS-induced colitis model was used in this study. Mice
received DSS for 5 days followed by oral treatment with LMT503 or
tofacitinib from day 5 when DSS was replaced by normal drinking water.
LMT503 treated mice showed alleviated body weight loss, which was
comparable to an IBD therapeutic JAK-inhibitor tofacitinib (Figure 2a)
(Sandborn et al., 2014). LMT503 treated mice also showed reduced disease
activity index (Figure 2b), recovered colon length (Figure 2c), and
bacterial translocation in mesenteric lymph nodes compared to mice in
the vehicle control group (Figure 2d). H&E staining of colon tissues
showed reduced inflammation in LMT503 treated groups (Figure 2e).
Pro-inflammatory cytokines TNF, MCP-1, and IL-1β were also significantly
reduced in LMT503 treated groups (Figure 2f).
To further evaluate inflammation in colon tissues, innate immune cell
infiltration was analyzed. Percentage and absolute numbers of
CD11b+Ly6G+ neutrophils and
CD11b+Ly6C+ monocytes were decreased
significantly in LMT503 treated groups (Figure 3a-d). However,
macrophage and dendritic cell percentage did not differ between LMT503
treated groups and vehicle control groups (Figures 3e,f and Figure
S1a,b).